Laboratory Studies
The laboratory evaluation of lymphadenopathy must be directed by the history and physical examination and is based on the size and other characteristics of the nodes and the overall clinical assessment of the patient. When a laboratory evaluation is indicated, it must be driven by the clinical evaluation. [1]
The following studies should be considered for chronic lymphadenopathy (>3 wk):
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CBC, including a careful evaluation of the peripheral blood smear
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Lactate dehydrogenase (LDH) and uric acid
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Chest radiography
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B henselae (catscratch) serology if exposed to a cat
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Tuberculosis skin test (TST) and interferon-gamma release assay (eg, Quantiferon Gold)
Evaluation of hepatic and renal function and a urine analysis are useful in identifying underlying systemic disorders that may be associated with lymphadenopathy. When evaluating specific regional adenopathy, lymph node aspirate for culture may be important if lymphadenitis is clinically suspected.
Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, cytomegalovirus (CMV), Toxoplasma species, and human immunodeficiency virus (HIV).
Imaging Studies
Chest radiography may be helpful in elucidating mediastinal adenopathy and underlying diseases affecting the lungs, including tuberculosis, coccidioidomycosis, lymphomas, neuroblastoma, histiocytoses, and Gaucher disease. [2]
Supraclavicular adenopathy, with its high associated rate of serious underlying disease, may be an indication for computed tomography (CT) scanning of the chest, abdomen, or both.
A retrospective study by Razek et al suggested that diffusion-weighted magnetic resonance imaging (MRI) can be used to differentiate malignant from benign mediastinal lymphadenopathy in children, with the mean apparent diffusion coefficient (ADC) for the former being significantly below that of the latter. [20] However, this was a small pilot with 29 patients, and the technique is not recommended for routine use.
Positron-emission tomography (PET) scanning is not helpful as a screening tool as benign and malignant conditions may cause intense uptake. [21] However, PET scanning is helpful in the staging of lymphomas once a diagnosis is made. [22]
Ultrasonography may be helpful in documenting the extent of lymph node involvement and any changes in the lymph nodes. [23] In children with inguinal adenopathy or abdominal complaints, ultrasonography or CT scanning of the abdomen (or both) may be indicated. [24] Due to its easy availability and noninvasive nature, there is increasing interest in using ultrasonography to better characterize the underlying cause of cervical lymphadenopathy; a retrospective study of 242 children found that the following were significant predictors of the differential diagnosis: perinodal fat hyperechogenicity, lymph node echogenicity, and short diameter of the largest lymph node. [25] More technically sophisticated techniques such as the intranodal vascularity index [26] and shear-wave elastography (SWE) [27] have been used to distinguish benign from malignant superficial lymphadenopathy; however, these are not in routine use.
Procedures
The critical question is often whether or not to perform a lymph node biopsy; this requires an overall assessment of the history and physical examination as described above.
Images taken during and after a lymph node biopsy are shown below.
A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.
A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
Treatment with antibiotics covering bacterial pathogens frequently implicated in lymphadenitis, followed by reevaluation in 2-4 weeks is reasonable, if clinical findings suggest lymphadenitis. Benign reactive adenopathy may be safely observed for months. [8]
If the size, location, or character of the lymphadenopathy suggests malignancy, the need for laboratory studies and biopsy is more urgent. If laboratory testing is inconclusive, a lymph node biopsy is immediately indicated.
While excisional biopsy is considered the "gold standard," it still has limitations and may yield a definitive diagnosis in only 40-60% of patients because of inadequate specimen size, improper handling, or node-sampling error (eg, Hodgkin lymphoma); sampling more accessible nodes may miss the underlying malignancy. The surgeon should therefore biopsy larger, firmer, and most recently enlarging nodes, even if it is technically difficult, with appropriate handling of the specimen. If an excisional biopsy does not reveal the diagnosis, a second biopsy may be indicated.
Fine-needle aspiration and core needle biopsy have become increasingly popular but yield small samples with limited ability to be assessed through flow cytometry and chromosomal analysis; also, false negative rates of 33% or higher have been found. [28] Retrospective studies by Wilczynski et al suggested that ultrasonographically guided full-core needle biopsy (UFCNB) is an effective alternative to whole surgical lymph node excision in lymphadenopathy of unknown origin if there is a low suspicion of malignancy. [29] Similarily, Sher-Locketz et al reported that fine-needle aspiration biopsy was an acceptable replacement for surgical biopsy in the triage of pediatric lymphadenopathy [30] )
Endobronchial ultrasonographically guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes; unfortunately, less than half will result in diagnostic cytology. [31] A multicenter study by Dhooria et al indicated that in adults, EBUS-TBNA and endoscopic ultrasonography with echobronchoscope-guided fine-needle aspiration (EUS-B-FNA) can be safely used in children with mediastinal lymphadenopathy, with a diagnostic yield of 57%. [32]
Histologic Findings
Histiologic findings depend on the underlying etiology of the lymphadenopathy. Nonspecific changes consistent with reactive adenopathy are often the only findings. This is helpful in ruling out malignancy, histiocytoses, granulomatous disorders, and storage diseases. Specific infections can be diagnosed if tissues are appropriately stained.
When examining the tissue, histiologic findings are often inadequate. Flow cytometric and chromosomal analysis may provide critical information to permit a diagnosis to be established.
Staging
Staging is relevant only when a specific malignancy is diagnosed as the etiology of lymphadenopathy.
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A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.
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A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
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A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
